Biology subjects

Quesnel, A.

Publications and source records attributed to Quesnel, A..

3 recordsLinked to original sources

bioRxiv2026

Establishment of a cochlear lymphatic vascular network and immune surveillance system following cochlear implantation

Hearing loss is a highly prevalent sensory abnormality often addressed with cochlear implants (CI) that provide auditory rehabilitation for deaf patients. However, a universal inflammatory foreign body response (FBR) to the implanted materials negatively impacts CI outcomes. The mechanistic basis for immune cell infiltration and propagation of the FBR directed against CIs is not defined. Using mouse CI models and quantitative, highly tractable reporters for lymphatics, blood vessels, and immune cells, we identify inner ear lymphatic vessels and changes to the immune surveillance system following cochlear implantation. Histopathological analysis of implanted temporal bones from human subjects shows that both blood vessels and lymphatics are evident within the scala tympani of the implanted cochlea. Our data reveal a rich lymphatic vascular network in the inner ear, closely associated with the perilymphatic and endolymphatic spaces. Lymphatics proliferate within the perilymphatic space of the implanted cochleae and appear to traffic immune cells. Together, our data provide direct evidence that concurrent proliferation of blood vessels and recruitment of blood-borne immune cells comprise an 'immune surveillance system' in the implanted cochleae that promotes the FBR. Our findings also highlight potential opportunities to limit adverse FBR outcomes following cochlear implantation.

systems biology↗

bioRxiv2024

Intratumoral CXCL12 Gradients Contextualize Tumor Cell Invasion, Migration and Immune Suppression in Breast Cancer

Although the CXCL12/CXCR4 pathway has been prior investigated for its prometastatic and immuno- suppressive roles in the tumor microenvironment, evidence on the spatiotemporal regulation of these hallmarks has been lacking. Here, we demonstrate that CXCL12 forms a gradient specifically around cancer cell intravasation doorways, also known as Tumor Microenvironment of Metastasis (TMEM) doorways, thus facilitating the chemotactic translocation of prometastatic tumor cells expressing CXCR4 toward the perivascular TMEM doorways for subsequent entry into peripheral circulation. Fur- thermore, we demonstrate that the CXCL12-rich micro-environment around TMEM doorways may cre- ate immunosuppressive niches, whereby CD8+ T cells, despite being attracted to these regions, often exhibit reduced effector functions, limiting their efficacy. While the CXCL12/CXCR4 pathway can mini- mally influence the overall composition of immune cell populations, it biases the distribution of CD8+ T cells away from TMEM doorways, justifying its prior-established role as immunosuppressive factor for CD8+ T cells. Our research suggests that the complex interactions between CXCL12 and the various tumor and immune cell types contributes not only to the completion of the initial steps of the metastatic cascade, but also offers an immunological "sanctuary" to prometastatic tumor cells homed around TMEM doorways. Overall, our study enhances our current understanding on the mechanisms, via which CXCL12 orchestrates tumor cell behavior and immune dynamics, potentially guiding future thera- peutic strategies to combat breast cancer metastasis and improve anti-tumor immunity.

cancer biology↗

bioRxiv2020

osr1 couples intermediate mesoderm cell fate with temporal dynamics of vessel progenitor cell differentiation

Transcriptional regulatory networks refine gene expression boundaries throughout embryonic development to define the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that establish the boundary between the IM and its neighboring vessel progenitors are poorly understood. Here, we delineate new roles for the zinc finger transcription factor Osr1 in kidney and vessel progenitor development. Zebrafish osr1 mutants display decreased IM formation and premature emergence of neighboring lateral vessel progenitors (LVPs). These phenotypes contrast with the increased IM and absent LVPs observed with loss of the bHLH transcription factor Hand2, and loss of hand2 partially suppresses the osr1 mutant phenotypes. hand2 and osr1 are both expressed in the posterior lateral mesoderm, but osr1 expression decreases dramatically prior to LVP emergence. Overexpressing osr1 inhibits LVP development while enhancing IM formation. Together, our data demonstrate that osr1 modulates both the extent of IM formation and the temporal dynamics of LVP development, suggesting that a balance between levels of osr1 and hand2 expression is essential to demarcate the dimensions of kidney and vessel progenitor territories. SUMMARY STATEMENTAnalysis of the osr1 mutant phenotype reveals roles in determining the extent of intermediate mesoderm formation while inhibiting premature differentiation of neighboring vessel progenitors.

developmental biology↗